Intranasal ERT in LSDs may bypass BBB

• May 13th, 2012

According to the study by Wolf et al. intranasal administration of α-l-iduronidase (IDUA) enzyme may be able to bypass the blood-brain barrier. This appears to be the case in IDUA-deficient mice after a single intranasal treatment with concentrated Aldurazyme®. Promising results in mice were also noted after intranasal treatment with an adeno-associated virus (AAV) vector expressing human IDUA. These experiments raise the possibility of non-invasive treatments for lysosomal storage disorders.

Lysosomal enzyme can bypass the blood-brain barrier and reach the CNS following intranasal administration. Wolf et al. Mol Genet Metab. 2012 May;106(1):131-4. PMID: 22420937 http://dx.doi.org/10.1016/j.ymgme.2012.02.006

posted by Yannis Trakadis MD, MSc

Mutations in histone acetyltransferase KAT6B cause Genitopatellar syndrome.

• March 20th, 2012

Sorry to blow my own horn but I’m quite passionate about the findings described below. Late last year, the group of Clayton-Smith et al. identified mutations in KAT6B in Ohdo syndrome, a condition characterized by blepharophimosis and developmental delay.

Shortly after, our group and the group of Simpson et al. identified mutations in the same gene in Genitopatellar syndrome, characterized by genital and patellar anomalies.

The developmental roles of this histone acetyltransferase are only beginning to be understood but it seems quite important for neurogenesis and skeletal development. The genotype-phenotype correlations are also fascinating. Both conditions are caused by de novo truncating mutations. While there is clinical overlap between the two conditions, there are also many differences, and there seems to be a clustering of the mutations which cause Genitopatellar syndrome. We are currently exploring the correlations and the impact of the mutations on the protein.

http://www.ncbi.nlm.nih.gov/pubmed/22077973
http://www.ncbi.nlm.nih.gov/pubmed/22265014
http://www.ncbi.nlm.nih.gov/pubmed/22265017

Posted by Philippe Campeau, MD

ERT and adult Pompe disease outcome

• February 24th, 2012

Regnery et al (2012) performed an open-label observational study of alglucosidase alfa enzyme replacement therapy (ERT) in 38 adult patients with GSD2. The patients first presented with the disease at a mean age of 36.2 ± 10.5 years but ERT treatment was only started after  14.5 ± 7.2 years (mean delay). This study demonstrates a variable course of neuromuscular deficits during the 36 months of this observational study (36 months of ERT treatment).

36 months observational clinical study of 38 adult Pompe disease patients under alglucosidase alfa enzyme replacement therapy. Regnery et al. J Inherit Metab Dis. 2012 Jan 31. [Epub ahead of print] PMID: 22290025

posted by Yannis Trakadis MD, MSc

Involvement of Bardet-Biedl proteins in neural crest cell migration

• May 6th, 2008

Proc Natl Acad Sci U S A. 2008 Apr 28 [Epub ahead of print]

Inhibition of neural crest migration underlies craniofacial dysmorphology and Hirschsprung’s disease in Bardet-Biedl syndrome.

Tobin JL, Di Franco M, Eichers E, May-Simera H, Garcia M, Yan J, Quinlan R, Justice MJ, Hennekam RC, Briscoe J, Tada M, Mayor R, Burns AJ, Lupski JR, Hammond P, Beales PL.

In this publication, the authors combine data from facial dysmorphology modeling, with experiments in mice and zebrafish to demonstrate their hypothesis that the proteins mutated in Bardet-Biedl syndrome are involved in neural crest cell migration.

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Click this link to see the most recent online abstracts of major genetics journals.

Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator

• August 25th, 2007

A group led by Orly Elpeleg has identified a gene associated with pontocerebellar hypoplasia, a heterogenous group of conditions.

Deleterious Mutation in the Mitochondrial ArginylTransfer RNA Synthetase Gene Is Associated with Pontocerebellar Hypoplasia
Simon Edvardson, Avraham Shaag, Olga Kolesnikova, John Moshe Gomori, Ivan Tarassov, Tom Einbinder, Ann Saada, and Orly Elpeleg
The American Journal of Human Genetics, volume 81 (2007),   
Thank you very much in advance for your contributions to this blog (Click on login to register and post a comment).

Click this link to see the most recent online abstracts of major genetics journals.
Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator

The human disease network

• July 20th, 2007

Combining the efforts of great minds in the field of network science and medical genetics, this paper describes the diseasome, an integrated network of genetic disorders.

See figure 13 for a great overview of some allelic conditions.

Goh KI, Cusick ME, Valle D, Childs B, Vidal M, Barabasi AL.
The human disease network.
Proc Natl Acad Sci U S A. 2007 May 22;104(21):8685-90

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Click this link to see the most recent online abstracts of major genetics.

Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator

Microdeletion 17q21.31 syndrome

• September 5th, 2006

In the September 2006 issue of Nature Genetics, three groups identify a new microdeletion syndrome (microdeletion 17q21.31). The major clinical features of this syndrome are severe hypotonia and moderate mental retardation
See the News and Views article by James R. Lupski:

Nat Genet. 2006 Sep;38(9):974-6.

Genome structural variation and sporadic disease traits.

Lupski JR.

James R. Lupski is in the Department of Molecular and Human Genetics and the
Department of Pediatrics, Baylor College of Medicine and Texas Children’s
Hospital, Houston, Texas, USA.
See also the artcles by Koolen DA et al., Shaw-Smith C et al. and Sharp J et al.

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Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator

Syndroc

• June 7th, 2006

Syndroc is a searchable online database describing frequent dysmorphic syndromes. It was designed by Daniel F. Schorderet. It can be a useful adjunct to OMIM, Possum, and the  Winter-Baraitser Dysmorphology Database.

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Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator

New Bardet-Biedl syndrome gene

• May 31st, 2006

Nat Genet. 2006 May;38(5):521-4. Epub 2006 Apr 2.
BBS10 encodes a vertebrate-specific chaperonin-like protein and is a major BBS
locus.
Stoetzel C. et al.

This french group identified a new gene mutated in up to 20% of the patients with Bardet-Biedl syndrome.

For information on retinitis pigmentosa which affects patients with Bardet-Biedl syndrome, please see chapter 235.

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Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator

Abase: Anthropometry on handheld computers

• May 14th, 2006

This free powerful tool for handheld computers (PDAs), devised by Andreas Zankl, permits you to plot anthropometric data on your hand held (height, weight, head circumference, eyes, ears, nose, mouth, chest, hands, feet). It compares your values to accepted reference values for USA, Canada, UK or Switzerland. The results are displayed in centiles, standard deviations or graphs. It is a must have for the busy geneticist.

Please visit www.medgen.unizh.ch/abase/ for more information.

Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator